Cyanidin-3-o-glucoside (C3G) inhibits vascular leakage regulated by microglial activation in early diabetic retinopathy and neovascularization in advanced diabetic retinopathy

Abstract

ABSTRACT Cyanidin-3-O-glucoside (C3G) is a kind of anthocyanin which shows strong anti-inflammation, anti-tumor and anti-oxidant properties. This paper was designed to explore the potential effects of C3G on diabetic retinopathy (DR). C57BL/6 mice were administrated with streptozotocin (STZ) or vehicle control for the establishment of diabetic models. To simulate hyperglycemia and hypoxia, D-glucose (30 mM) and CoCl2 (200 μm/l) were utilized to treat HRECs, respectively. The migration, invasion, inflammation and tube formation abilities of cells were evaluated with the adoption of wound healing, transwell, ELISA and tube formation assays, respectively. Besides, immunofluorescence staining was utilized to detect proliferation and retinal vessels. Evans blue permeation assay were performed to evaluate the vascular leakage in DR mice. Moreover, western blot and qPCR were used to quantify the mRNA and protein expressions of ionized calcium-binding adapter molecule (Iba)-1 and tight junction proteins. Results showed that C3G alleviated the inflammation, microglial activation and angiogenesis in DR mice. Moreover, the proliferation and inflammation of BV2 cells induced by high glucose (HG) were suppressed by C3G. Evans blue permeation assay demonstrated the potency of C3G in attenuating vascular leakage. In addition, C3G suppressed the migration, invasion and angiogenesis of human retinal endothelial cells (HRECs) DR model in vitro. By confirming the role of C3G in inhibiting vascular leakage regulated by microglia activation in early DR and angiogenesis in advanced DR, this study pointed out the potential of C3G as a therapeutic drug for DR management.